Method and apparatus for sensing a property of a fluid

ABSTRACT

A device for sensing a property of a fluid comprising a first substrate having formed thereon a sensor configured in use to come into contact with a fluid in order to sense a property of the fluid, and a wireless transmitter for transmitting data over a wireless data link and a second substrate having formed thereon a wireless receiver for receiving data transmitted over said wireless link by said wireless transmitter. The first substrate is fixed to or within said second substrate. Additionally or alternatively, the device comprises a first substrate defining one or more microfluidic structures for receiving a fluid to be sensed and a second substrate comprising or having attached thereto a multiplicity of fluid sensors, the number of sensors being greater than the number of microfluidic structures. The second substrate is in contact with the first substrate such that at least one of the sensors is aligned with the or each microfluidic structure so as to provide an active sensor for the or each structure, and such that one or more of the sensors is or are not aligned with any microfluidic structure and is or are thereby redundant.

FIELD OF THE INVENTION

The present invention relates to methods and apparatus for sensing aproperty of a fluid. In particular, the invention provides coordinationof sensors in a microfluidic environment.

BACKGROUND

Devices that integrate one or several functions on a single chip havemany applications such as monitoring a property of a fluid or a chemicalreaction. Such devices, known as lab-on-chip devices, typically combinesemiconductor sensors and microfluidic channels on a tiny scale.

However, there is a requirement for low-cost integration of differenttechnologies, in particular CMOS/MEMS and microfluidics.Economies-of-scale especially driven by the semiconductor industryfavour solutions based on unmodified commercial processes. Theconstraints dictated by the varying range of physical dimensions of thedifferent components make wafer-level integration too costly forlow-cost mass manufacture. For example, a typical Lab-on-Chipapplication may require CMOS components having an area in the region of1-10 mm², MEMS components in the region of 25-100 mm² and microfluidicscomponents in the region of 200-2500 mm². Therefore integrating these atwafer level would be hugely wasteful to CMOS/MEMS technologies, as thecommon Lab-on-Chip area would be dominated by the requirements ofinterfacing fluids and external systems to the devices.

FIG. 1 of the accompanying drawings shows a cross-section of hybridCMOS/microfluidics composite having bond-wires 10 and die 4 encapsulatedusing photo-patternable epoxy 2. The microfluidic chamber 11 is formedby the substrate 1 being fixed to the carrier substrate 8. Problemsarise in wire-bonding the fine bond wires and the need to encapsulatethem afterwards.

Encapsulating chips at die level typically requires depositing andprocessing photosensitive materials (such as certain epoxies and SU-8)onto composite assemblies (such as a package or substrate), which arewire-bonded to the die (see FIG. 1 of the accompanying drawings). Acommon challenge is to avoid damage to delicate bond-wires due tomechanical stress caused by fluid viscosity in addition to centrifugalforces in spin-coating. An alternative approach is to define theunexposed (i.e. chemical sensitive) area via a sacrificial material (eg.SU-8), or by accurately defining a frame and then potting the regionbetween the frame and package using a UV-curable epoxy. This techniqueis often referred to as “Dam and Fill” encapsulation. Commercialchemical sensors use more complex process flows based on combining theabove techniques with pre-fabricated housings to ensure robust isolationin addition to long-term stability. However these are very laborious andthus expensive to mass-produce. All these above-mentioned techniqueshowever have two fundamental limitations: (i) an unwanted well(typically 200-300 μm depth) is formed inside the bondpad regions, and(ii) due to this relatively thick encapsulant build-up, the top surfaceis not perfectly planar. This causes sealing, adhesion, and alignmentproblems when overlaying microfluidic channels above, which oftenrequires an intermediate levelling step.

Several technology-based packaging solutions have been proposed. Howeverthese typically require post-processing CMOS devices at wafer scale(i.e. before dicing). Flip-chip packaging methods can provide a robustlyencapsulated, planar top surface, however the issue of “parasitic wells”above the chip surface is not overcome. The MIT/Lincoln Labsexperimental 3D CMOS process based on multiple Silicon-on-Insulator(SOI) CMOS tiers allows for through-tier vias and since the silicon sitson an insulating substrate, the bondpads can be brought to the undersideof the substrate, leaving the top-layer planar for chemical sensingpurposes. This perhaps offers the most promising solution for futureemerging technologies (expected to feature towards the end of Moore'slaw—when scaling from 22 nm to 10 nm). This is confirmed by IBMdedicating a complete issue to 3D CMOS in their flagship “IBM Journal ofResearch & Development”. However, this technology remains years frombeing commercially available, and even then is expected to remainrelatively expensive (compared to bulk CMOS) and thus it will be limitedto niche applications.

Once the sensor has been encapsulated, it is desirable to provide amicrofluidic channel to bring the fluid to the sensor. These channelsare typically formed in a substrate, which is separate from the sensorsubstrate. The two substrates are aligned and sealed to each other. Assemiconductor sensors become progressively smaller with a finer pitch,there arise problems with aligning the microfluidic channels to thesensors. Poor assembly tolerances mean that there is a chance that thewalls between the channels may obstruct a sensor and indeed there maynot be a sensor in each channel. In mass production, microfluidicalignment tolerances may be 100-1000 times more than the minimum featuresize of the sensor.

In some applications it may be desirable to monitor reactions in anumber of fluidic chambers using ISFET sensors. It is desirable topattern a number of ISFET sensors on a single silicon chip, and yet havedifferent reactions happen above each sensor. This means that thesurface of the chip must be encapsulated in such a way as to createmultiple chambers which are fluidically sealed from each other so thattheir chemical components cannot intermix.

To provide a seal between sensors, it is expected that a layer offluidic channels/chambers will be mounted on top of the electronic chip.This could be built or etched directly on the surface of the chip withphotolithography, or alternatively could be built as a separate part viaa variety of means and then attached to the chip as a subsequent step.

Either way, an apparent trade-off is created as the fluidicchannels/chambers must be aligned to the sensors. There is incentive tomake the sensors closely spaced, i.e. fine-pitched, to minimise the sizeand therefore cost of the silicon chip (and fluidics as well). However,there is a competing incentive to make the sensors further apart so thatit is simpler to produce the fluidics and align them with the sensors.

Substrates are often aligned by either aligning one substrate to a datumline on the other (perhaps a physical protrusion) or by aligningvisually overlapping marks on each substrate. The intention is that thetwo substrates are centre aligned or normally aligned, such that thechambers and sensors are symmetrically aligned about a centre line(s).This usually means that the midpoint of each sensor is aligned to themidpoint of each chamber. Thus the alignment tolerance from centre isusually the width of the chamber less the sensor width, after whichpoint a portion of the sensing surface will not be exposed to thechamber. The alignment tolerance may be expressed as:

Tolerance=±(Wc−Ws)/2  (1)

Where Wc,Ws represent respectively the Width of one chamber, Width ofone sensor.

The following references provide background to lab-on-chip packaging:

U.S. Pat. No. 7,033,910: Method of fabricating multi layer MEMS andmicrofluidic devices on a substrate with layers of predetermined weakand strong bond regions, communication provided by edge interconnectsbetween layers

U.S. Pat. No. 6,910,268: Method for fabricating an IC interconnectsystem including an in-street integrated circuit wafer via. Notwireless, uses wired vias.

U.S. Pat. No. 7,207,728: Optical bond-wire interconnections and a methodfor fabrication thereof. Optical bond-wire interconnections betweenmicroelectronic chips, wherein optical wires are bonded ontomicroelectronic chips.

U.S. Pat. No. 6,443,179: Packaging of electro-microfluidic devices.Electrical connection is made to bond pads on the front of the MIC.

U.S. Pat. No. 6,531,342: Method for transverse hybrid loc package

U.S. Pat. No. 6,882,033: High density direct connect LOC assembly

U.S. Pat. No. 6,136,212: Polymer-based micro-machining for microfluidicdevices

(WO/2003/107043) OPTOELECTRONIC ASSEMBLY WITH EMBEDDED OPTICAL ANDELECTRICAL COMPONENTS.

IPC8 Class: AH05K714FI, USPC Class: 361796: Interconnection andPackaging Method for Biomedical Devices with Electronic and FluidFunctions

E. Culurciello et. Al, “Capacitive Inter-Chip Data & Power Transfer for3-D VLSI”, IEEE TCAS-II, Vol. 53, No. 12, 2006.

T. D. Strong, “Integrated Electrochemical Neurosensors”, IEEE ISCAS'06,pp. 4110-4113, 2006.

W. Oelβner, et al., “Encapsulation of ISFET sensor chips”, Sensors &Actuators B, Vol. 105, pp. 104-117, 2005.

L. Sudakov-Boreysha et al., “ISFET CMOS Compatible Design andEncapsulation Challenges”, IEEE Conference on Electronics, Circuits andSystems (ICECS'04), pp. 535-538, 2004.

“3D Chip Technology”, IBM Journal of Research and Development, Vol. 52,No. 6, 2008.

Vilches A, Sanni A, Toumazou C, Single coil pair transcutaneous energyand data transceiver for low power bio-implant use, IET ELECTRONICSLETTERS, 2009, Vol: 45, Pages: 727-U25, ISSN: 0013-5194.

It is an object of the present to provide apparatuses and methodsovercoming the problems with the present techniques as discussed above.

SUMMARY OF THE INVENTION

According to a first aspect of the invention there is provided a devicefor sensing a property of a fluid, the device comprising a firstsubstrate having formed thereon a sensor configured in use to come intocontact with a fluid in order to sense a property of the fluid, and awireless transmitter for transmitting data over a wireless data link;and a second substrate having formed thereon a wireless receiver forreceiving data transmitted over said wireless link by said wirelesstransmitter. The first substrate is fixed to or within said secondsubstrate.

According to a second aspect of the invention there is provided a methodof operating one or more sensors and comprising the steps of providing afluid in contact with a sensor, powering the sensor and transmitterusing a transducer, sensing a property of the fluid using the sensor,and wirelessly transmitting sensed or processed sensed data using atransmitter.

According to a third aspect of the invention there is provided a methodof fabricating a microfluidic sensor device comprising the steps ofproviding a first substrate defining one or more microfluidic structuresfor receiving a fluid to be sensed, providing a second substratecomprising or having attached thereto a multiplicity of fluid sensors,the number of sensors being greater than the number of microfluidicstructures, and fixing the first and second substrates together suchthat at least one of the sensors is aligned with the or eachmicrofluidic structure so as to provide an active sensor for the or eachstructure, and such that one or more of the sensors is or are notaligned with any microfluidic structure and is or are thereby redundant.

According to a fourth aspect of the invention there is provided a devicecomprising a first substrate defining one or more microfluidicstructures for receiving a fluid to be sensed and a second substratecomprising or having attached thereto a multiplicity of fluid sensors,the number of sensors being greater than the number of microfluidicstructures. The second substrate is in contact with the first substratesuch that at least one of the sensors is aligned with the or eachmicrofluidic structure so as to provide an active sensor for the or eachstructure, and such that one or more of the sensors is or are notaligned with any microfluidic structure and is or are thereby redundant.

According to a fifth aspect of the invention there is provided a methodof configuring a device and comprising the steps of (i) detecting afirst signal corresponding to a first sensor and (ii) determining whichsensors are exposed to which microfluidic structure using the firstsignal and knowledge of a property of the fluid of at least onemicrofluidic structure or knowledge of the spatial relationship amongthe sensors.

According to a sixth aspect of the invention there is provided aconfiguration apparatus for configuring a device, the configurationapparatus comprising (i) a receiver for detecting a first signalcorresponding to a first sensor and (ii) means for determining whichsensors are exposed to which microfluidic structure using knowledge of aproperty of the fluid in at least one of the microfluidic structures orknowledge of the spatial relationship among the sensors.

Preferred embodiments are set out in the accompanying dependent claims.

DESCRIPTION OF DRAWINGS

Specific embodiments of the invention will now be described by way ofexample only, with reference to the accompanying figures, in which:

FIG. 1 is a known CMOS encapsulation method for chemical sensing;

FIG. 2 is a cross-section of a microfluidic assembly with a CMOS sensorembedded within a substrate;

FIG. 3 illustrates an embodiment providing data transfer using optical(IR) communication;

FIG. 4 illustrates an embodiment providing data transfer using localinductive coupling;

FIG. 5 illustrates an embodiment providing data transfer using RFIDtechnology;

FIG. 6 illustrates a two-dimensional array of fluid chambers overlayinga two-dimensional array of ISFETs; and

FIG. 7 illustrates a one-dimensional array of fluid chambers overlayinga one-dimensional array of ISFETs.

DETAILED DESCRIPTION

In one embodiment, illustrated by FIG. 2, a semiconductor sensor chip 13is encapsulated by adhesive 15 within a recess of substrate 16. Thisleaves the sensing surface of the chip co-planar with the chamber 12. Asecond substrate 14 is sealingly fixed to the substrate 16 and providesmicrofluidic channels for the fluid to be sensed.

Fluid may be brought into contact with the sensing surface of chip 13and detected. Properties such as temperature, pH, chemistry, flowconductivity, etc. may be detected by an appropriate sensor integratedinto the chip. By providing suitable wireless communication andtransducer hardware on the CMOS chip, a scheme for contactless power anddata transfer can be implemented. The chip is thus capable of wirelesslytransmitting a signal to a receiver located nearby. The signal containsdata relating to the state of the chip or a property of the fluid viathe sensor.

The embodiment thus provides a method of encapsulating and interfacing asensor chip to a device without any bond-wires leaving the chip's topsurface planar.

A transducer is a device for transforming energy from one form toanother. For example, a circuit may receive incident radiated energy andtransform it into a DC electrical power. In such a way power may betransmitted wirelessly.

Wireless communication refers to communication amongst two or moredevices without the use of electrically conducting wires, as is typicalof conventional communication methods. The transmission of wirelesscommunication may be provided by energizing a signal which emanates fromthe transmitter or modulating an energized signal passing near orthrough the transmitter to create a new signal. The signal containscoded or uncoded data that can be interpreted by a receiver. Thecommunication may be two-way in which case each device is configured totransmit and receive signals (a transceiver). A first device may producea energy burst to request data (by polling or ‘pinging’) from a seconddevice such that the second device then transmits data.

A wireless scheme may be applied to a Lab-on-Chip (LOC) assembly byimplementing the following design steps:

-   -   Fit a CMOS die within a recess of a (carrier) substrate, which        may be a multi-layer printed circuit board (PCB), such that the        top surfaces of the die and (carrier) substrate are co-planar        (see FIG. 2).    -   Stack a microfluidic substrate onto the carrier substrate. These        can be designed to be of equal dimensions (i.e. length and        width), to form a 2-layer assembly (see FIG. 2).    -   Provide a communication subsystem and transducer on the CMOS        chip to recover power and data from an external source, in        addition to being able to transmit data off-chip.    -   Provide suitable structures, for example, PCB patterned antennas        or inductors into the (carrier) substrate or sub-miniature        surface mount (chip) components (depending on the wireless        technique chosen) embedded within the carrier substrate.    -   Provide a ground plate on the underside (obverse of the sensing        surface) of the die which contacts a ground plate of the        substrate for the purpose of providing an electrical ground for        the die. The contacts may be bonded together by electrically        conducting epoxy, which also serves to mechanically couple the        die to the substrate.

Such a device has advantages of reliability, cost reduction, and ease ofassembly.

A wireless sensor system arrangement alleviates the requirement forwire-bonding thus providing substantial cost benefits for massmanufacture. In addition to direct savings relating to wire-bondprocessing, additional processing steps are saved, for example bond-wireencapsulation and surface levelling steps. As the encapsulant around thebond wires is typically the first component to degrade when immersed inan electrolyte, the stability and reliability of the chip are alsoimproved. The semiconductor chip itself, which requires expensivematerial and processing, may be much smaller than before as no space isrequired for bonding or encapsulation. The chip may be as small as thesensor and communication hardware.

Simplifying the process flow alleviates the requirement fortime-intensive high precision alignment tasks. This means the variouscomponents can be manufactured to utilise inexpensive mass productiontechniques, for example injection moulding and robot assembly. Assemblyalignment issue are reduced because the sensor chips may be droppeddirectly into the microfluidic chambers (which is physically larger thanthe chip itself) without the need to align the substrates exactly. Theremay be many chambers formed in a substrate, with one or more chipslocated within each chamber.

This method avoids the formation of parasitic wells formed withinencapsulated dies (via traditional methods). This simplifies themicrofluidic channel design, in addition to providing a means for robustsubstrate integration due to inherently planar substrates.

FIG. 1 identifies the following components:

1. Microfluidic substrate

2. Encapsulant

3. Bondpad (on chip)

4. Die (i.e. chip)

5. Silicon substrate

6. Dielectric/Passivation

7. Parasitic microfluidic well

8. Carrier substrate (e.g. PCB)

9. Bondpad (on carrier substrate)

10. Bondwire

11. Microfluidic channel

FIG. 2 identifies the following components:

12. Microfluidic channel

13. Die (i.e. chip)

14. Microfluidic substrate

15. Adhesive/encapsulant

16. Carrier substrate (e.g. PCB)

FIG. 3 identifies the following components:

17. Carrier substrate (e.g. PCB)

18. Light emitter

32. Light detector

33. Reflector (e.g. sheet of interconnect metal)

34. Silicon substrate

35. Reflected light path

36. Optical modulator

37. Die (i.e. chip)

FIG. 4 identifies the following components:

19. Inductive coupling

20. Inductor on carrier substrate

21. Inductor on chip

28. Carrier substrate (e.g. PCB)

29. Silicon substrate

30. dielectric stack/interconnects

31. Die (i.e. chip)

FIG. 5 identifies the following components:

22. Die (i.e. chip)

23. Antenna on chip

24. Silicon substrate

25. Antenna on carrier substrate

26. Carrier substrate (e.g. PCB)

27. RF communication

FIGS. 3 to 5 illustrate embodiments for achieving power and datatransfer (between the CMOS die and the substrate), replacing physicalwire bonds with wireless methods. The figures illustrate: (FIG. 3) useof an optical emitter from the underside to power the device and use ofelectro-optical techniques to modulate the reflected signal; (FIG. 4) aninductive power/data transfer between on-chip and PCB inductors; and(FIG. 5) use of RF wireless technology.

The wireless power/data transfer can, for example, be achieved using thethree following techniques:

Optoelectronic transmission: Optoelectronics is the application ofelectronic devices that source, detect and control light, for example byabsorption and modulation of optical energy. By embedding the integratedcircuit within a substrate that incorporates suitable optoelectroniccomponents, power can be transmitted to the integrated circuit (IC) anddata received from it, providing the appropriate hardware is integratedwithin the IC. More specifically this would require integrating a solarcell to recover optical power, in addition to an optical emitter ormodulator for transmitting the sensor data. One method of achieving thelatter is by modulating free-carrier absorption through reverse biasinga pn-junction (see UK patent application 1001696.2). This scheme isillustrated in FIG. 3. The carrier substrate (17) houses an opticalemitter (18), optical detector (32) and integrated circuit (37). Byirradiating a modulator (36) designed within the bulk silicon (34), theresulting beam of light (35) can be modulated by adjusting theabsorption within the modulator. The resulting beam can be reflected tothe underside of the IC using a metallic reflector (33). Thisadditionally acts to double the modulation effect (by modulating thelight twice—the incident and return path).

Near field: Near field wireless transmission techniques work overdistances comparable to, or a few times the diameter of the device(s),and up to around a quarter of the wavelengths used. Near field transferis usually magnetic (inductive), but electric (capacitive) energytransfer can also occur.

Power and data can alternatively be transmitted wirelessly throughinductive coupling between an on-chip inductor and patterned inductorembedded within the carrier substrate. This is illustrated in FIG. 4.The integrated circuit (31) incorporates the sensor, interfaceelectronics and integrated inductor (21). The integrated inductor isdesigned using appropriate geometries of metallic interconnects (30)within the chip. This is inductively coupled (19) to a secondaryinductor (20) embedded within the carrier substrate (28) designed suchas to maximize the coupling efficiency (e.g. in close proximity, matchedquality factors, etc.). The integrated circuit (31) and carriersubstrate (28) are also required to include all necessary components tofacilitate the inductive transfer of power and data via standard circuittopologies.

Far Field: Far field methods achieve longer ranges, often multiplekilometre ranges, where the distance is much greater than the diameterof the device(s). With Electo-Magnetic propagation, signals may betransmitted from multiple integrated circuits within a single carriersubstrate employing far-field (e.g. traditional RF) transmission ofpower and data. Within each integrated circuit (22), an integratedantenna (23) is included in addition to a standard RF transceivercircuit. The carrier substrate (26) includes an embedded antenna (25)which is shared by all IC's by transmitting a carrier wave from thesubstrate antenna (25), receiving this on the integrated antennas (23)and rectifying the AC signal to recover a DC power supply. Data istransmitted from the independent chips back to the carrier byimplementing on-chip RF transmitters. Multiple channels (for multiplechips) can be multiplexed by using standard RF communication techniques(time-division, frequency division, etc. multiplexing). The system caneither use a shared set of antennas for power and data transmission orseparate elements to improve the efficiency of each task (i.e. power anddata transfer).

Thru-Fluid Propagation: A signal can be transmitted through the fluid.It is well-known that a water solution which includes salt, or any othereffective electrolyte, acts as a conductive medium, and therefore can beused to send information on the same principle as a wire. Oneillustrative implementation is to have a chip with an integral electrode(e.g. silver/silver chloride or other means) which contacts the fluid,allowing the circuitry on the chip to interface with the potential ofthe fluid and/or vice-versa. A second electronic module in communicationwith the chip would also have an electrode contacting the sameelectrolyte. Any voltage or voltage change driven by an electrode oneither module would be conducted to the other module by the fluid,thereby influencing the other electrode being measured at the receiver.In this way, voltage changes could act as a signal for analogue ordigital information to be sent between the modules via the potential ofthe fluid. An alternative to direct electrode contact is tocapacitively-couple the chip to the fluid (for example, if a metal tracein the chip was separated from direct contact with the fluid by chippassivation) or by other non-contact means.

Further, if it is desirable for the fluid to also act as a stable DCbias (as in the case of a potentiometric measurement), then thecircuitry, electrodes, and or signals, can be designed such as to onlyaffect the potential of the fluid within a particular frequency rangewhich does not interfere with the DC bias. Generally, having anon-zero-impedance coupling between the electrode and the fluid, orbetween the driving circuit and the electrode, in at least one frequencyband, is one way to ensure that the driving circuit can influence thefluid's potential without completely excluding the influence of othersources. This would enable 2-way communication, or multiplexing ofmultiple sources (e.g. via different frequency ranges or many otherknown techniques for multiplexing RF signals). One such implementationwould be to have a capacitor in series between the driving circuit andthe reference electrode in order to act as a high-pass filter, allowingthe DC potential to be set externally by a reference electrode or anyother module in the system (which correspondingly may have a low-passfilter with non-zero source impedance at some frequencies in its drivingcircuit to allow the electrolyte's potential to be driven at relativelyhigher-frequency for data communication). Another enhancement would befor the chip to connect both driving and receiving circuits to itselectrode via non-zero and non-infinite impedances, such that both sendand receive functions are possible. Tri-state buffers can be used tofurther eliminate the influence of the driving circuit when notdesirable.

The above embodiments differ from prior art wireless devices in severalrespects:

-   -   The wireless elements are all combined in a monolithic        integrated circuit (IC), as opposed to being implemented using        one or more discrete components (eg. off-chip antenna, inductor,        etc.    -   The integrated circuit (IC) contains no bondpads or bondwire        connections, whereas other devices are wireless in one aspect        but still rely on bondwires in other aspects, for example        between the chip and package for power supply or off-chip        discrete components.    -   The transmitter and receiver communicate wirelessly whilst being        physically connected. The distance between them is also        predetermined and substantially fixed. Typically the reason for        using wireless technology is because the transmitter and        receiver are physically separated and occupy positions that        change or are unknown.

In one embodiment, a fluid is introduced into a chamber of the deviceand brought into contact with the sensor surface. The sensor is used todetect a property of the fluid or monitor a reaction within the fluid.This property may be the temperature or ion concentration. The carriersubstrate may be constantly powering the device and/or waiting toreceive a signal. The chip could transmit the present sensor value,possibly after performing signal processing. Alternatively the substratewould transmit power at a desired time which would power up the sensorchip. The chip may send the signal immediately or wait until it receivesa request for the signal. For example, there may be several sensorsmonitoring separate fluids and the device could poll or ping theindividual sensors at predetermined times.

The power transmitter, signal transmitter, and signal receiver may beformed on the same substrate or separated. For example the substratesmay be plugged as a cartridge into an In Vitro Device having circuitrywhich receives, analyses, and displays the sensor value.

Preferably the chip is monolithic comprising the sensor(s), transducer,and transmitter circuitry. Therefore there is provided an integratedchip having no wires between the chip and a substrate.

In one preferred embodiment there is a chip in physical contact with andwirelessly communicating with a PCB substrate. The chip has:

-   -   A receiving coil with a tuning capacitor to impedance-match the        transmitting coil and optimise the quality factor.    -   An asynchronous rectifier to rectify the output of the receiving        coil to give a stable DC output voltage (1.4 V with 0.1 V        ripple).    -   A clock recovery circuit in the form of a phase-locked loop        (PLL) which comprises a voltage-controlled oscillator (VCO), a        phase detector, and a loop filter. This produces a clock signal        synchronized with the transmitting frequency.    -   A BPSK demodulator which uses the aforementioned on-chip        recovered clock signal and the voltage across the receiving coil        to produce the demodulated bitstream.

The PCB substrate has a transmitting coil driven with a 60 Vpeak-to-peak drive voltage in the 2.4 GHz unlicensed band. The data iscoded onto this voltage using binary phase-shift keying (BPSK) such thatthe driving amplitude, and hence the power transmitted to the chip, isconstant

Data is transmitted from the chip to the PCB via the on-chip “receiving”coil to the PCB “transmitting” coil (i.e., there are no separate coils). This is done via load-shift keying (LSK) in which the load the on-chipcoil sees is changed. This causes the current oscillating in the PCBcoil to change, which can easily be measured and demodulated.

In a further embodiment, microfluidic structures are finely-spacedwithout requiring fine alignment, by building redundancy into the systemby creating an array of ISFETs which are greater in number than themicrofluidic structures themselves. Then, within wide tolerance inlateral alignment, the redundancy ensures that wherever eachmicrofluidic structure aligns during assembly, at least one ISFET willbe available at an appropriate location to measure it. The ISFETs whichalign with the microfluidic structures are utilised and the ones thatare buried under walls are not.

In an embodiment, illustrated by FIG. 6 a, an array of sensors 42 arefixed to one substrate, and a second substrate 40 comprising an array ofmicrofluidic chambers 41 is aligned and sealed to the first substrate.The sealing prevents fluids from one chamber entering another chamber.In order to provide a robust assembly procedure, there are more sensorsthan chambers, the sensor being arranged such that relative misalignmentof the two substrates still results in at least part of one sensingsurface exposed to the fluid in each chamber.

As can be seen from FIG. 6 a, chambers 41 a illustrate the case wherechambers are well aligned with one whole sensor each. However thesubstrates may be relatively misaligned in the X and/or Y direction suchthat each chamber (indicated by dashed chambers 41 b) is aligned with adifferent sensor, or portions of several sensors.

The amount of movement permissible in the plane of the substrate willdepend largely on the number of excess sensors and pitch of the sensors.In FIG. 6 a, the sensor pitch is equal to the width of the chamberallowing the greatest amount of movement whilst ensuring that eachchamber is aligned with a whole sensor or portions of several sensors.This arrangement is suitable to sensors that do not require that theentire sensing surface be exposed to the fluid in order to make ameasurement.

For sensors that require that the entire sensing surface be exposed tothe fluid, it will be desirable to decrease the pitch of the sensors. Asseen in FIG. 6 b, each chamber aligns with at least one whole sensor andpossibly portions of additional sensors. In this arrangement it ispossible to have a chamber aligned with 4 whole sensors, the sensorpitch arranged such that the sensor pitch plus one sensor width is lessthan or equal to the chamber width.

It is possible that in addition to alignment tolerance, one wouldconsider the manufacturing tolerances of the chambers or sensors. Forexample the chamber array may be irregularly spaced apart or havediffering chamber widths. The combination of these tolerances should beconsidered when determining the sensor layout. In particular, thealignment tolerance will affect the number of excess sensors needed andthe manufacturing tolerance will affect the sensor pitch needed.

The array may be one dimensional (see FIG. 7) or two dimensional (seeFIG. 6). In FIG. 7, the chambers are part of channels in which a fluidflows (as indicated by the vertical arrows 53). The fluid flow isperpendicular to the sensor array. Movement in the Y-direction has noaffect on the sensor-chamber relationship and movement in theX-direction results in a change in the sensor-chamber relationshipaccounted for by the excess of sensors.

In the embodiment illustrated in FIG. 7, two chambers having a width(51) of 200 um and a pitch (54) of 400 um, intersect a linear array of50 um-wide ISFETs having a pitch (52) of 150 um. There are 9 sensors,providing an excess of 7 sensors. The channels need not be alignedbetter than ±475 um from the centre line (allowing a total lateralmovement of 950 um) to ensure a whole sensor is exposed to each chamber.Such a tolerance is much improved over the typical device having asingle, cantered sensor per chamber where the tolerance would be ±75 nm.However, by adjusting the parameters, even finer channels could bealigned with even less precision. The general expression for thetolerances given by:

Total_Tol=(Ns−1)*Ps−Ws−(Nc−1)*Pc+Wc  (2)

±Tot=±Total_Tol/2  (3)

where:

-   -   Wc, Ws Width of one chamber, Width of one sensor    -   Pc, Ps Pitch of chambers, Pitch of sensors    -   Ns, Nc Number of sensors, Number of chambers    -   Total_Tol, ±Tol Total allowable lateral movement, alignment        tolerance in each direction from centre line

An advantage is that this technique decouples the competing prioritiesof high sensor density and simplicity of assembly, so that fine-pitchsensors and chambers can be employed to minimise chip cost withoutrequiring expensive, fine-scale assembly and alignment.

Certain embodiments may include one or more of the following properties:

-   -   the transverse separation distance between adjacent sensors        surfaces is less than the width of chamber in that direction;    -   there is a greater number of sensors than number of chambers,        preferably 10% more or 2 more;    -   there is a greater number of sensors than number of chambers,        preferably 50% more or 5 more;    -   there is a greater number of sensors than number of chambers,        preferably 100% more or 10 more;    -   there is at least one sensor at least partly exposed to each        chamber and at least one sensor is not wholly exposed to any        chamber;    -   the width of a chamber is greater than or equal to the pitch of        the sensors;    -   the pitch of the sensors is less than the pitch of the chambers;    -   the pitch of the chambers is twice the pitch of the sensors;    -   the pitch of the sensors is less than width of the chambers plus        the width of the sensors;    -   the total width of the sensor layout is wider than the width of        the chamber layout;    -   one substrate is aligned to the other substrate within a        predetermined tolerance depending on the number of sensors in        excess of the number of chambers.

After assembly, it may be initially unknown as to which sensors arecovered by the second substrate and which sensors are exposed and towhich chamber. Similarly it may be initially unknown which wirelesssensors are paired with which receiver on the substrate and locatedwithin which chamber The arrangement can become known during ancalibration step with controlled conditions to see which sensorsmeasurements are different from the rest. For example, exposedtemperature sensors will detect the temperature of the fluid in thechambers whilst blocked sensors will detect the temperature of thesubstrate. A controlled temperature may be introduced into the substrateor one or more chambers to highlight the difference in sensormeasurements. To select an active ISFET, one could change the potentialor composition of the fluid electrolyte and observe which ISFETs react.Those that do not react beyond a predetermined threshold are consideredto be unexposed to the fluid.

In one embodiment, several wireless sensors communicate with a far fieldtransceiver in the substrate and the identity of each sensor in eachchamber is unknown. A property of the fluid in each chamber is alteredsuch that the fluids do not all have the same property in each chamber.For example, a heater in each chamber may be turned on one at a time, ora temperature gradient across the chambers may be established.Alternatively an electrode exposed to the fluid may provide a referencevoltage to be detected. The substrate transceiver requests a signal froma particular sensor. This can be repeated for each sensor. The signalsof the sensors are compared to each other or to the properties of eachchamber fluid to determine which sensors are aligned with whichchambers.

Some sensor arrangements will not require controlled conditions. Forexample, some sensors will output different signals depending on whetherthey are exposed to a chamber or to the second substrate.

In another embodiment, the relationship between sensors and chamber isdetermined from the known geometries of the sensor pattern (or substratereceiver pattern) and chamber pattern. Preferably, the signal of thesensor outermost in the array is observed first, moving progressivelyinwards to detect which is the first signal exposed to a chamber. Forexample, in FIG. 6 a, the bottom-leftmost sensor which appears to beactive is determined to be aligned with the bottom-leftmost chamber, theremaining relationships becoming apparent after that. A sensor that isone chamber pitch separated from a known active sensor is likely to beactive as well.

In the case where more than one sensor is aligned with a chamber,several active signals from neighbouring sensors will confirm thelocation of the chamber. The sensor measurements may be used tocalculate an average, detect a faulty sensor, or provide measurementredundancy. The plurality of sensors exposed to a chamber may alsoprovide spatio-temporal imagery.

The above calibration steps may be performed using software or hardware.The results of the calibration may be stored in a look up table toidentify active sensors and their location for future signal processing.The steps may be performed as an assembly step or during the initialoperation of the lab-on-chip.

In the above discussions a fluid is exposed to the sensors by providinga chamber for containing the fluid. The skilled person will appreciatethat other microfluidic structures may also provide an appropriate formfor exposing the fluid to the sensors such as a channel for directingthe fluid across the sensors, a well for holding a fluid, or even asimple substrate for receiving a droplet contained by surface tension.The term “microfluidic” generally refers to the manipulation of fluidsthat are geometrically constrained to a small, typically sub-millimetre,scale.

It should be appreciated that features described herein and illustratedin the attached drawings may be incorporated alone or in appropriatecombination with other features. For example, different technologies forpowering and transmitting signals may be combined to create a wirelesssensing system.

1-28. (canceled)
 29. A device for sensing a property of a fluid, thedevice comprising: (i) a first substrate having formed thereon a sensorconfigured in use to come into contact with a fluid in order to sense aproperty of the fluid, and a wireless transmitter for transmitting dataover a wireless data link and (ii) a second substrate having formedthereon a wireless receiver for receiving data transmitted over saidwireless link by said wireless transmitter; wherein said first substrateis fixed to or within said second substrate.
 30. The device of claim 29,said first substrate comprising a transducer for transducing receivedelectromagnetic radiation to provide electrical energy for poweringcomponents of the first substrate.
 31. The device of claim 29, saidfirst substrate being bonded to said second substrate, preferably usingan adhesive.
 32. The device of claim 29, wherein said first substrate isa semiconductor die comprising integrated circuits which at least inpart provide said sensor and said wireless transmitter.
 33. The deviceof claim 29, wherein said second substrate comprises a multi-layerprinted circuit board.
 34. The device of claim 29, wherein there are nobond wires connecting the first substrate to the second substrate. 35.The device of claim 29, wherein the first substrate has further formedthereon a wireless receiver for receiving data transmitted by atransmitter formed on the second substrate.
 36. The device of claim 29,wherein the wireless data link is provided using one of far fieldtransmission, near field transmission, optoelectric transmission, ortransmission through the fluid using voltage modulated by an electrodeintegrated with the first substrate.
 37. The device of claim 29 andcomprising a microfluidic structure for locating said fluid onto asensing surface of said sensor.
 38. The device of claim 37, wherein saidmicrofluidic structure is formed by a third substrate bonded to one orboth of said first and second substrates.
 39. The device of claim 29,further comprising a plurality of said first substrates and a pluralityof microfluidic structures for locating said fluid onto a sensingsurface of each sensor, each first substrate arranged to wirelesslycommunicate with the receiver on said second substrate.
 40. A method ofoperating a device of claim 29, the method comprising: (a) providing afluid in contact with the sensor, (b) sensing a property of the fluidusing the sensor, and (c) wirelessly transmitting the sensed orprocessed sensed data using the transmitter.
 41. The method according toclaim 41, further comprising depositing a micro-volume of a fluid sampleto a substrate comprising the microfluidic structure.
 42. The methodaccording to claim 41, wherein the data is transmitted substantiallycontinuously.
 43. The method according to claim 41, further comprisingreceiving a request signal at the first substrate and transmitting datafrom the first substrate in response to the request signal.
 44. Themethod according to claim 43, wherein the request signal identifies thedata, first substrate, and/or sensor from which data is requested.
 45. Amethod of fabricating a microfluidic sensor device comprising: (a)providing a first substrate defining a plurality of microfluidicstructures for receiving a fluid to be sensed; (b) providing a secondsubstrate comprising or having attached thereto a multiplicity of fluidsensors, the number of sensors being greater than the number ofmicrofluidic structures; and (c) fixing the first and second substratestogether such that at least one of the sensors is aligned with eachmicrofluidic structure so as to provide an active sensor for eachstructure, and such that one or more of the sensors is or are notaligned with any microfluidic structure and is or are thereby redundant.46. The method according to claim 45, wherein misalignment of the firstsubstrate to the second substrate by an amount equal to one sensor pitchfrom a centre alignment position still results in at least one sensoraligned within each microfluidic structure.
 47. The method according toclaim 45, wherein misalignment of the first substrate to the secondsubstrate by an amount greater or equal to one channel pitch stillresults in at least one sensor aligned within each microfluidicstructure.
 48. The method according to claim 45, wherein the fluid is abiological or chemical sample to be monitored or detected.
 49. A devicecomprising: (i) a first substrate defining a plurality of microfluidicstructures for receiving a fluid to be sensed and (ii) a secondsubstrate comprising or having attached thereto a multiplicity of fluidsensors, the number of sensors being greater than the number ofmicrofluidic structures; wherein the second substrate is in contact withthe first substrate such that at least one of the sensors is alignedwith each microfluidic structure so as to provide an active sensor foreach structure, and such that one or more of the sensors is or are notaligned with any microfluidic structure and is or are thereby redundant.50. The device of claim 49, wherein a distance between adjacent sensorsis less than a width of each microfluidic structure.
 51. The device ofclaim 49, wherein the spatial density of sensors is greater than thespatial density of microfluidic structures.
 52. The device of claim 49,wherein the sensors are arranged as an array of sensors and themicrofluidic structures are arranged as an array of microfluidicstructures.
 53. The device of claim 52, wherein a width of the sensorarray is wider than a width of the microfluidic structure array.
 54. Thedevice of claim 52, wherein a pitch of the microfluidic structure arrayis at least twice a pitch of the sensors array.
 55. The device of claim52, wherein a pitch of the sensor array is less than the width of themicrofluidic structure.
 56. A method of configuring a device of claim48, the method comprising: (a) detecting a first signal corresponding toa first sensor and (b) determining which sensors are exposed to whichmicrofluidic structure using the first signal and knowledge of aproperty of the fluid of at least one microfluidic structure orknowledge of the spatial relationship among the sensors.
 57. The methodaccording to claim 56, further comprising the step of processing thefirst signal before proceeding to (b) by comparing the first signal to apredetermined value or to a second signal corresponding to a secondsensor.
 58. The method according to claim 56, further comprisingaltering the property of the fluid in one or more microfluidicstructure.
 59. The method according to claim 58, wherein the property ofthe fluid in each microfluidic structure is altered one microfluidicstructure at a time.
 60. The method according to claim 56, furthercomprising performing (a) and (b) for a plurality of the sensors. 61.The method according to claim 60, wherein (a) and (b) are firstperformed with a sensor located at an extreme of a sensor array, thenrepeated with sensors that are located progressively inwards.
 62. Themethod according to claim 56, further comprising the step of determiningwhich sensors are not exposed to a microfluidic structure.
 63. Themethod according to claim 56, further comprising creating a look uptable identifying which sensors correspond to which microfluidicstructures as a result of (b).
 64. A configuration apparatus forconfiguring a device of claim 48, the apparatus comprising: (i) areceiver for detecting a first signal corresponding to a first sensorand (ii) means for determining which sensors are exposed to whichmicrofluidic structure using knowledge of a property of the fluid in atleast one of the microfluidic structures or knowledge of the spatialrelationship among the sensors.
 65. The configuration apparatus of claim62, further comprising means for altering the property of the fluid inat least one microfluidic structure.
 66. The configuration apparatus ofclaim 65, further comprising a memory for storing a result of (ii).